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Brewer W.J.,University of Melbourne | Lambert T.J.,Brain and Mind Research Institute | Witt K.,University of Melbourne | Dileo J.,Murdoch Childrens Research Institute | And 4 more authors.
The Lancet Psychiatry | Year: 2015

Background: The first episode of psychosis is a crucial period when early intervention can alter the trajectory of the young person's ongoing mental health and general functioning. After an investigation into completed suicides in the Early Psychosis Prevention and Intervention Centre (EPPIC) programme, the intensive case management subprogramme was developed in 2003 to provide assertive outreach to young people having a first episode of psychosis who are at high risk owing to risk to self or others, disengagement, or suboptimal recovery. We report intensive case management model development, characterise the target cohort, and report on outcomes compared with EPPIC treatment as usual. Methods: Inclusion criteria, staff support, referral pathways, clinical review processes, models of engagement and care, and risk management protocols are described. We compared 120 consecutive referrals with 50 EPPIC treatment as usual patients (age 15-24 years) in a naturalistic stratified quasi-experimental real-world design. Key performance indicators of service use plus engagement and suicide attempts were compared between EPPIC treatment as usual and intensive case management, and psychosocial and clinical measures were compared between intensive case management referral and discharge. Findings: Referrals were predominately unemployed males with low levels of functioning and educational attainment. They were characterised by a family history of mental illness, migration and early separation, with substantial trauma, history of violence, and forensic attention. Intensive case management improved psychopathology and psychosocial outcomes in high-risk patients and reduced risk ratings, admissions, bed days, and crisis contacts. Interpretation: Characterisation of intensive case management patients validated the clinical research focus and identified a first episode of psychosis high-risk subgroup. In a real-world study, implementation of an intensive case management stream within a well-established first episode of psychosis service showed significant improvement in key service outcomes. Further analysis is needed to determine cost savings and effects on psychosocial outcomes. Targeting intensive case management services to high-risk patients with unmet needs should reduce the distress associated with pathways to care for patients, their families, and the community. Funding: National Health & Medical Research Council and the Colonial Foundation. © 2015 Elsevier Ltd.

Karl T.,Neuroscience Research Australia | Karl T.,Schizophrenia Research Institute | Cheng D.,Neuroscience Research Australia | Garner B.,University of Wollongong | And 2 more authors.
Expert Opinion on Therapeutic Targets | Year: 2012

Introduction: Dementia currently affects over 35 million people worldwide. The most common form of dementia is Alzheimer's disease (AD). Currently, treatments for AD do not stop or reverse the progression of the disease and they are accompanied by side effects. Areas covered: The main features of AD pathology, treatment options currently available, the endocannabinoid system and its functionality in general and its role in AD pathology in detail will be outlined. A particular focus will be on the therapeutic potential of the phytocannabinoid cannabidiol. Expert opinion: Based on the complex pathology of AD, a preventative, multimodal drug approach targeting a combination of pathological AD symptoms appears ideal. Importantly, cannabinoids show anti-inflammatory, neuroprotective and antioxidant properties and have immunosuppressive effects. Thus, the cannabinoid system should be a prime target for AD therapy. The cannabinoid receptor 2 appears to be a promising candidate but its role in AD has to be investigated cautiously. Furthermore, the phytocannabinoid cannabidiol is of particular interest as it lacks the psychoactive and cognition-impairing properties of other cannabinoids. In conclusion, future research should focus on the evaluation of the effects of manipulations to the endocannabinoid system in established animal models for AD, combined with early-phase studies in humans. © Informa UK, Ltd.

Hardy T.A.,University of Sydney | Hardy T.A.,Brain and Mind Research Institute | Miller D.H.,University College London
The Lancet Neurology | Year: 2014

Baló's concentric sclerosis is often regarded as a rare variant of multiple sclerosis. Patients with this disorder present with acute or subacute neurological deterioration, with MRI showing one or more concentrically multilayered ring-like lesions usually in the cerebral white matter. Historically, Baló's concentric sclerosis was thought fatal in all cases. However, the availability of MRI has led to a better appreciation of the variable natural history of patients presenting with radiologically evident Baló lesions and the clinical association with multiple sclerosis and, less often, with other neurological disorders. Important advances have increased understanding of the immunopathogenic mechanisms associated with the formation of Baló lesions. However, how to treat an acute lesion and when or whether to start treatment are less well understood, although for patients with Baló lesions who also fulfil standard diagnostic criteria for multiple sclerosis, our opinion is that treatment with multiple sclerosis disease-modifying therapy would seem reasonable. © 2014 Elsevier Ltd.

Sethi S.,University of Sydney | Campbell A.J.,University of Sydney | Ellis L.A.,Brain and Mind Research Institute
Journal of Technology in Human Services | Year: 2010

Despite the efficacy of cognitive-behavioral therapy (CBT) in treating adolescent anxiety, few sufferers seek treatment. Barriers to accessing psychologists include a shortage of skilled therapists, long waiting lists, and affordability. The Internet is a medium possibly able to address issues of accessibility and affordability. This study aimed to assess the efficacy of online therapy in the treatment and prevention of adolescent anxiety and depression. Participants (N1/438) were randomly allocated to one of four conditions: online CBT, face-to-face CBT, combined face-to-face=online CBT, and control. Combined face-to-face=online CBT is more effective in treating symptoms of depression and anxiety compared to stand-alone online or face-to-face therapy. The present study suggests that for those who are unable to access face-to-face therapy, computerized therapy may be a viable option. This is an important finding, especially in light of current capacity to treat and accessibility problems faced in the treatment of adolescent depression and anxiety. © Taylor & Francis Group, LLC.

Bukhari W.,Griffith University | Barnett M.H.,Brain and Mind Research Institute | Prain K.,Autoimmune laboratory | Broadley S.A.,Griffith University
International Journal of Molecular Sciences | Year: 2012

Neuromyelitis optica (NMO) is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG) against aquaporin-4 (AQP4), a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS) when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6) have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies. © 2012 by the authors; licensee MDPI, Basel, Switzerland.

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